Niacin formulations and methods with reduced flushing side effect

Abstract

Compositions and methods for reducing the flushing effect (cutaneous erythema) of niacin and for treating hyper lipemia and elevated triglycerides, comprising a prenylflavonoid, such as xanthohumol, and niacin (nicotinic acid or Vitamin B3).

What is claimed is: 
     
         1 . A pharmaceutical composition with hypolipemic or hypotryglyceridemic amounts of niacin having reduced capacity to provoke a flushing reaction in a subject, comprising a hypolipemic or hypotryglyceridemic amount of niacin, and a prenylflavonoid. 
     
     
         2 . The composition of  claim 1 , wherein the prenylflavonoid is a prenylflavonone. 
     
     
         3 . The composition of  claim 1 , wherein the prenylflavonoid is a prenylchalcone. 
     
     
         4 . The composition of  claim 1 , wherein the prenylflavonoid is selected from the group consisting of xanthohumol, xanthogalenol, desmethylxanthohumol (2′,4′,6′,4-tetrahydrooxy-3-C-prenylchalcone), 2′,4′,6′,4-tetrahydrooxy-3′-C-geranylchalcone, dehydrocycloxanthohumol, dehydrocycloxanthohumol hydrate, 5′-prenylxanthohumol, tetrahydroxanthohumol, 4′-O-5′-C-diprenylxanthohumol, chalconaringenin, isoxanthohumol, 6-prenylnaringenin, 8-prenylnaringenin, 6,8-diprenylnaringenin, 4′,6′-dimethoxy-2′,4-dihydroxychalcone, 4′-O-methylxanthohumol, 6-geranylnaringenin, 8-geranylnaringenin, metabolites thereof, derivatives thereof, and combinations thereof. 
     
     
         5 . The composition of  claim 1 , wherein the prenylflavonoid is xanthohumol, a xanthohumol metabolite, or a xanthohumol derivative. 
     
     
         6 . The composition of  claim 5 , wherein the composition includes from 0.5 mg to 1000 mg of xanthohumol. 
     
     
         7 . The composition of  claim 5 , wherein the composition includes from 5 mg to 250 mg of xanthohumol. 
     
     
         8 . The composition of  claim 5 , wherein the composition includes from 10 mg to 50 mg of xanthohumol. 
     
     
         9 . The composition of  claim 1 , wherein the prenylflavonoid is present in an amount suitable to at least partially alleviate flushing induced by the niacin in a majority of human subjects. 
     
     
         10 . The composition of  claim 1 , wherein the prenylflavonoid is present in an amount suitable to completely alleviate flushing induced by the niacin in a majority of human subjects. 
     
     
         11 . The composition of  claim 1 , wherein the amount of niacin is 50 mg to 4,000 mg. 
     
     
         12 . The composition of  claim 1 , wherein the amount of niacin is 500 mg to 2,000 mg. 
     
     
         13 . The composition of  claim 1 , wherein the niacin is in a sustained-release dosage form. 
     
     
         14 . The composition of  claim 1 , wherein the amount of niacin is both a hypolipemic and a hypotryglyceridemic amount of niacin. 
     
     
         15 . A method of suppressing cutaneous erythema in a patient to whom niacin is administered, comprising administering to the patient an amount of xanthohumol sufficient to reduce flushing prior to or concurrently with the administration of niacin. 
     
     
         16 . The method of  claim 15 , wherein the amount of xanthohumol is from 1 mg to 500 mg, and the amount of niacin is from 50 mg to 4,000 mg. 
     
     
         17 . The method of  claim 15 , wherein the amount of xanthohumol is from 5 mg to 50 mg, and the amount of niacin is from 500 mg to 2,000 mg. 
     
     
         18 . The method of  claim 15 , wherein the niacin is in sustained-release dosage form. 
     
     
         19 . The method of  claim 15 , wherein the xanthohumol is administered prior to the niacin. 
     
     
         20 . The method of  claim 19 , wherein the xanthohumol is administered at least 1 hour prior to the niacin being administered so as to be released in or be absorbed by the patient prior to initial administration of the niacin. 
     
     
         21 . The method of  claim 15 , wherein the xanthohumol is administered concurrently with the niacin. 
     
     
         22 . A composition for treating dyslipidemia and hypertryclyceridemia, comprising an effective amount of niacin to treat dyalipidemia or hypertryglyceridemia, and xanthohumol in an amount effective to reduce cutaneous erythma caused by the effective amount of niacin. 
     
     
         23 . The composition of  claim 22 , wherein the xanthohumol is in immediate release form and the niacin is in sustained-release or delayed release dosage form. 
     
     
         24 . A pharmaceutical composition for administration of HDL elevating or hypotriglyceridemic amounts of niacin having reduced capacity to provoke a flushing reaction in a subject, comprising water soluble xanthohumol and sustained-release niacin. 
     
     
         25 . A method of reducing or shortening the early titration phase of niacin dosing, wherein a first dose can be accelerated to at least 500 mg of sustained-release or immediate release niacin on a first day, and a subsequent titrations can be advanced to 1,000 mg of niacin on a second day and 1,500 mg on a third day, wherein, on the first day, a pre-dose of xanthohumol is administered at least 30 minutes prior to said first dose of niacin, and thereafter prior to or concurrently with higher doses of niacin.